Camptothecin (hereinafter described as CPT) isolated from the bark, root, fruit, leaf and the like of Camtotheca acuminata of Chinese origin is a pentacyclic alkaloid and is known to show the anti-tumor activity by inhibition of a nucleic acid synthesis. In the meantime, as to a camptothecin derivative the induction of diarrhea and the like as a side effect are reported (Gann to Kagaku Ryohou 17, p 115–120, 1990), leaving a problem to cause disorder for the gastrointestinal tract, and therefore, various kinds of derivatives have been examined to reduce the toxicity, to increase the effect, and so on.
Thus, the inventors already reported 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin.hydrochloride.trihydrate (hereinafter described as CPT-11), the water soluble semisynthetic derivative of CPT, as a compound which is reduce in toxicity compared to CPT, and it is at present widely used as the anti-tumor agent (general name; irinotecan hydrochloride).
Camptothecin analogs such as CPT-11 can be derived by a chemical modification of CPT obtained from natural materials.
However, owing to an extremely low amount of CPT obtained from natural materials such as Camtotheca acuminata which is the starting material, it is anticipated that according to an increased demand of CPT-11 which is a useful derivative and the like, a sufficient supply of CPT becomes difficult notwithstanding a measure for the starting material supply such as afforestation. Although the total synthesis is also examined, it is the present situation that it has not yet been into practical use.
As a process by total synthesis is known the method of Shen, W. et al. represented by the below reaction scheme via Friedländer reaction of the aminopropiophenone and the tricyclic ketone (J. Org. Chem. 1993, 58, 611–617 “Concise Total Syntheses of dl-Camptothecin and Related Anticancer Drugs.”, though there are problems that the steps are tedious, the yields are not sufficient and only the racememate is synthesized.

In the meantime, although Curran, D. P. et al. carried out a total synthesis by the method using a cascade radical cyclization of the aryl isonitrile and the iodopyridone represented by the below reaction scheme (Chem. Eur. J. 1998, 4, 67–83 “A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles.”), problems are pointed out in which the yield of the cyclization reaction is not sufficient and deprotection of the protective group is necessary after cyclization.

Additionally, although the above Curran, D. P. et al. synthesized 4-iodo-2-methoxy-6-trimethylsilylpyridine-3-carbaldehyde, an intermediate in the synthesis of the tricyclic ketone part of CPT analogs, according to the below scheme,
this method is highly dangerous due to the necessity to use t-BuLi easily flammable in a large amount industrially, and the reaction at −78° C. as a reaction temperature is required, making it impossible to enlarge the batch size. Further, owing to the necessity of a complicated temperature control in the total reaction system it was not an industrially practical reaction system.